z Available online at http://www.journalcra.com INTERNATIONAL JOURNAL OF CURRENT RESEARCH International Journal of Current Research Vol. 9, Issue, 12, pp.62497-62502, December, 2017 ISSN: 0975-833X RESEARCH ARTICLE INCLUSION BODIES - A REVIEW 1Dr. Mrunalini Mahesh Dadpe, 2, *Dr. Sourab Kumar, 3Dr. Mahesh Dadpe, 4Dr. Payoshnee Bhalinge Jadhav, 5Dr. Abhishek Jadhav and 6Dr. Shilpi Suman 1, 4Department of Oral Pathology, M A Rangoonwala Dental College, Aazam Campus, Camp, Pune 411001, India 2, 5, 6Department of oral Pathology, D.Y. Patil School of Dentistry, Nerul, Navi Mumbai 400706, India 3MIDSR Dental College, Vishwanathpuram, Amba Jogai Road, Latur 413531, India ARTICLE INFO ABSTRACT Article History: The word inclusion means incorporation. Inclusion bodies are nuclear or cytoplasmic aggregates of Received 16th September, 2017 stainable substances which are usually ‘proteins’. They typically represent sites of viral multiplication Received in revised form in bacteria or in a eukaryotic cell and usually consist of viral capsid proteins. Inclusion bodies are 17th October, 2017 typically identified within a cell by their different appearance. Accepted 25th November, 2017 Published online 27th December, 2017 Key words: Proteins, Viral, Types, Structures Copyright © 2017, Mrunalini Mahesh Dadpe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Citation: Dr. Mrunalini Mahesh Dadpe, Dr. Sourab Kumar, Dr. Mahesh Dadpe, Dr. Payoshnee Bhalinge Jadhav, Dr. Abhishek Jadhav and Dr. Shilpi Suman, 2017. “Inclusion Bodies - A Review”, International Journal of Current Research, 9, (12), 62497-62502. Classification INTRODUCTION Viral inclusion bodies Inclusion bodies (IB) can also be hallmarks of genetic diseases, as in the case of Neuronal Inclusion bodies in neural disorders, A. Intracytoplasmic eosinophilic so basically they are Inactive Aggregates of protein known as Guarnieri bodies in Small pox Inclusion Bodies (IB). In order to identify the types and causes Henderson-Peterson bodies in Molluscum contagiosum of inclusion bodies in human cells, it is primarily important to Negri bodies in Rabies know what an inclusion body is. In simple terms, inclusion B. Intranuclear acidophilic- bodies are abnormal structures that appear in cells. They are Cowdry type A in Varicella zoster virus foreign invaders and unwelcomed in any living body. C. Intranuclear basophilic Owl eyes" in cytomegalovirus Significance of inclusion bodies (Salvador Ventura and D. Both intranuclear and intracytoplasmic- Antonio Villaverde, 2006) Warthin finkeldey bodies in Measles Mitsoid bodies in Heck’s disease Inclusion bodies are considered to be formed by unspecific hydrophobic interactions between Inclusion bodies in Erythrocytes disorderly deposited polypeptides and are observed as ‘molecular dust-balls’ in cells. Normally a red blood cell does not contain inclusions in the Identification of different diseased conditions. cytoplasm. It may be seen during certain hematologic disorders IBs can be a source of relatively pure protein because like they can be easily purified from disrupted cells. A. Developmental Organelles *Corresponding author: Dr. Sourab Kumar, Department of oral Pathology, D.Y. Patil School of Dentistry, Nerul, Howell-Jolly bodies Navi Mumbai 400706, India. Pappenheimer bodies 62498 Dr. Mrunalini Mahesh Dadpe et al. Inclusion bodies - A review Cabot Rings Basophilic stippling B. Abnormal Hemoglobin Precipitation Heinz bodies Haemoglobin H Inclusions Koilocytes – Term used generally to denote the viral inclusion cell especially for HPV. Large vacuolization in the cell is seen below the granular cell layer with basophilic inclusion bodies (Textbook of Oral Pathology). Henderson- Paterson bodies Smallpox pustules have been called “pearls of pus” to help distinguish them from the more delicate “dewdrops on rose petals,” which describes typical Varicella Zoster (Mike bray1 and mark buller, 2004). Histologically cutaneous smallpox lesions may resemble herpetic lesions except that smallpox has intracytoplasmic inclusions (Guarnieri bodies) also known as type-B inclusions. They are named after Italian physician Giuseppe Guarnieri, and appear in the cytoplasm of epithelial cells instead of intranuclear inclusions (Lipschutz bodies) of herpetic lesions (David et al., 2009). Fig 1. Cytological smear showing Koilocytes with double nucleus Henderson- Paterson bodies - Molluscum contagiosum (MC) Molluscum contagiosum (MC) is a viral infection of the skin or occasionally of the mucous membranes. It is caused by a DNA poxvirus called the molluscum contagiosum virus (MCV) MCV has no animal reservoir, infecting only humans. Molluscum contagiosum lesions are pearly in appearance with a dimpled centre. The central waxy core contains the virus. 2 These lesions appear microscopically as inverted lobules of hyperplastic acanthotic squamous epithelium which is seen Negri Bodies pushing into the underlying connective tissue. The center of endophytic bulbous structures are filled with enlarged, altered They are named after Adelchi Negri who first discovered them. keratinocytes with basophilic viral inclusions (intranuclear) These inclusion bodies are typically found in nerve cells that referred to as Henderson- Paterson bodies. These represent have been infected by the rabies virus. They probably stem the particles of pox virus in different stages of maturation. from outside influences which deliver rabies in the first place. Initially, the small viron particles are seen in a cytoplasm of the epithelial cell above basal layer. These eosinophilic Herpes simplex virus (HSV) particles enlarge at the level of granular layer and occupy the entire cell. In the superficial layers of epithelium, the large Herpes simplex virus infections are common vesicular cytoplasmic inclusion bodies are seen in the cells along with eruptions of the skin and mucosa. The virus-infected cresentic compressed nucleus. The Henderson- Paterson bodies keratinocytes contain one or more homogeneous, glassy are expelled at the center of the crater from the cells of stratum nuclear inclusions. These cells are readily found on cytological corneum. Foreign body reaction and inflammatory cells may preparations (Textbook of Pathology - Regezi). The virus be seen in relation to extrusion of bodies in underlying needs cells to replicate and thereby infect it. Over a period of connective tissue stroma. Molluscum contagiosum has been time the cell undergoes a structural and biochemical alterations reported to occur in association with neovascular nevus, a halo that ultimately lead to cell death. The cell death is usually due nevus and with lupus erythematosus (Textbook of Pathology – to response to infection and virus replication. The infected cell Saraf). shows enlarged nucleoli (ballooning) as earliest manifestation which is displaced towards nuclear membrane and eventually it Small pox (Guarnieri bodies) undergoes disaggregation and fragmentation. Small pox (Variola) Variola meaning “pimple” It is a life The host and other structural changes that are induced by virus threatening disorder and was declared that has been eradicated in the host cell are: by the World Health Organization in 1977. 62499 International Journal of Current Research, Vol. 9, Issue, 12, pp.62497-62502, December, 2017 Chromosomal margination. Duplication and folding of intracellular membrane. Fragmentation of golgi stacks. Insertation of viral proteins into cellular membranes. Polykaryocytosis – cell become round in shape and fuse with each other Rearrangement of microtubular network The light microscopy shows nuclear inclusions of an hour glass appearance. It takes an eosinophilic stain at a later stage. Imunofluroscent experiments using antibodies specific for HSV DNA have shown intranuclear foci and these enlarge to form globular structures and these are called as replication compartment analogus to translucent nuclear inclusion seen by electron and light microscopy. These replication compartments are located in the interior of nucleus, thus the accumulated replication proteins, progeny viral DNA, nucleocapsid may cause nuclear cytopathic effects described as nuclear inclusion effects. The infected cells also manifest acantholysis, such Warthin-Finkeldey cells are labelled as Tzanck cells (Textbook of Pathology – Saraf). "Owl eyes" inclusion bodies in cytomegalovirus Cytomegalovirus (from the Greek cyto- "cell" and -megalo "large") is commonly known as HCMV or Human Herpes virus 5 (HHV-5). HCMV infections are frequently associated with salivary glands though they may be found throughout the body. The infection rarely manifests intra orally in patient who are compromised. CMV infection can be demonstrated microscopically by the detection of intra nuclear inclusion bodies. On H&E staining the inclusion bodies stain dark pink and are called "owl's eye" inclusion bodies. Histological analysis of the biopsied lesion shows intranuclear inclusions and prominent nucleoli. These nuclear inclusions involve half of the nuclear diameter and usually set off from the nuclear membrane by a clear halo. Affected cells are strikingly enlarged often to a diameter of 40um in size and show cellular and nuclear polymorphism (Textbook of Pathology - Robbins) these cellular inclusions take up PAS stain and Gomori’s stain (Textbook of Pathology – Saraf). Balooning of